Title: The function(s) of AVP and PKC beta I in the SCN of mice Bidirectional selection for thermoregulatory nest-building behavior in house resulted in a 40-fold difference between the high-selected and low- skeletal lines (big and small nest-builders, respectively) in the amount of cotton used for a nest. Unexpectantly, this selection procedure also resulted in differences among the lines in several circadian rhythm parameters of wheel-running activity, which are highly reproducible from generation to generation. In addition, neuroanatomical studies indicated that the small nest-builders have a large number of arginine-vasopressing (AVP) neurons in the suprachiasmatic nuclei (SCN), the circadian clock in mammals, than the big nest-builders and non-selected control mice. Furthermore, the amount of protein kinase C betaI (PKCbetaI) immunoreactivity in the SCN is highest in the small nest builders and losers in the big nest-builders and non-selected control mice. The number of AVP and PKCbetaI neurons among the lines are positively correlated with measures of the strength of the circadian activity rhythm and negatively correlated with the level of thermoregulatory nest-building behavior. These lines represent a unique opportunity to investigate the functional role of AVP and PKCbetaI in the SCN by using within species differences in circadian and thermoregulatory behavior, and their anatomical and neurochemical correlates. We will test the central hypothesis that the SCN, through the functional roles of AVP and PKCbetaI, adapts animals to extreme environments by regulating circadian activity rhythms and thermoregulation. The following specific hypotheses will be tested to address this central hypothesis: 1. the SCN regulates the strength of circadian activity rhythms. 2. The SCN regulates the level of thermoregulatory nest-building behavior and body temperature (Tb). 3. Differences in the number of AVP neurons in the SCN among the selected lines result in different neurophysiological properties of the SCN in vivo. 4. PKCbetaI is part of a second messenger system that couples will be conducted as an integrated and coordinated collaboration between investigators at the University of Alaska Fairbanks and Columbia University. This work will contribute to the general understanding of how the circadian clock in mammals adapts individuals to the earth's day-night cycle and, therefore, advances issues related to human health, that include the deterioration of circadian function during aging and dementia, seasonal affective disorder, and the entrainment of the visually impaired to the day-night cycle.